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Background Intracerebral hemorrhage (ICH) is aggravated by immune cells that participate in the inflammatory response from the blood-brain barrier (BBB). O-Glycosylation has been reported to regulate the inflammatory response in the central nervous system but its cerebral protective effects remain unknown. Therefore, this study was carried out to investigate the protective effects of O-GlcNAcylation in a murine model of ICH and the possible mechanisms involved. Methods The effects of O-GlcNAcylation on hematoma and edema formation were tested using pathological and dry/wet weight methods, whereas its effects on neural function were determined using neurologic tests. The effect of O-GlcNAcylation on BBB integrity was determined by Evans blue dye extrusion. Flow cytometry was used to quantify the immune cells in the central nervous system. Immunofluorescence was used to detect the protective effect of O-GlcNAcylation in ICH. Results The hematoma volume was significantly lower in the prevention and treatment groups than in the control group after ICH induction, indicating that O-GlcNAcylation had reduced the formation of cerebral hematoma in ICH. In the prevention and treatment groups, the modified neurological severity score, corner turn test and rotating rod test results were improved and the BBB integrity was better than that in the control group. O-GlcNAcylation also regulated the microglia, neutrophils and other central nervous system immune cells after ICH, effectively reducing the inflammatory response. Conclusions O-GlcNAcylation played an important role in suppressing the inflammatory response, enhancing the BBB integrity and reducing edema after ICH.

Background: It is important to predict poststroke cognitive outcome to guide individualized treatment and prevention strategy. We aimed to evaluate the predictive value of the combination of a serum biomarker for axonal damage (neurofilament light chain [NfL]) and neuroimaging markers (volume of infarction and white matter hyperintensities [WMH]) for neuronal abnormality in poststroke cognitive outcome. Methods: A total of 1028 patients were screened; among them, 144 patients with acute ischemic stroke (stroke group) and 30 patients without stroke (control group) were enrolled. Serum NfL levels of samples obtained from both groups were measured through single molecule array assay. Neuroimaging markers of neuroaxonal injury, including infarct volume and WMH in the stroke group were quantified on magnetic resonance images using an in-house MATLAB code (MATLAB 2017; MathWorks). The primary outcome was the functional independence measure (FIM) cognitive subscores on discharge. We assessed the association of serum NfL levels and neuroimaging markers with cognitive outcome. The prognosis value of the combination of serum NfL levels and imaging markers for predicting FIM cognitive subscores on discharge was calculated using the area under curve (AUC) of the receiver operating characteristic. Results: Serum NfL levels of the stroke group were 9-fold higher than those of the control group (1449.7 vs 157.2 pg/mL, n = 144/30, P < .001). There was a correlation of serum NfL levels with infarct volume ( r = 0.530, P < .001) and functional outcome, including FIM cognitive subscores ( r = −0.387, P < .001) and FIM motor subscores on admission ( r = −0.306, P < .001), but not with WMH volume after adjusting for infarct volume ( r = −0.196, P = .245). Serum NfL levels on admission independently predicted poststroke FIM cognitive subscores on discharge (AUC = 0.672, P < .001). The predictive value for poststroke cognitive outcome was improved by combining serum NfL levels with infarct and WMH volume (AUC = 0.760, P < .001). Conclusion: The combination of serum NfL levels with volume of infarct and WMH shows an improved predictive value for cognitive function during acute rehabilitation phase after stroke, providing a promising panel of biomarkers for prognosis and guidance of treatment.

The first listing of hog futures provides farmers with new means of risk prevention, value preservation and income increase, but the factors affecting their willingness to participate in hog futures are worthy of in-depth analysis. Based on survey data in Sichuan Province, this paper uses the oprobit model to analyze the factors affecting farmers’ willingness to participate in hog futures. We finally find that education level, breeding cooperation, price stability, information channels, risk aversion, and futures training can significantly improve farmers’ willingness to participate in hog futures. On the contrary, income will significantly reduce farmers’ willingness to participate in hog futures. To the end, this paper puts forward relevant suggestions to help promote the implementation of hog futures.

Background Altered calcium homeostasis is hypothesized to underlie Alzheimer's disease (AD). However, it remains unclear whether serum calcium levels are genetically associated with AD risk. Objective To develop effective therapies, we should establish the causal link between serum calcium levels and AD. Methods Here, we performed a Mendelian randomization study to investigate the causal association of increased serum calcium levels with AD risk using the genetic variants from a large-scale serum calcium genome-wide association study (GWAS) dataset (61,079 individuals of European descent) and a large-scale AD GWAS dataset (54,162 individuals including 17,008 AD cases and 37,154 controls of European descent). Here, we selected the inverse-variance weighted (IVW) as the main analysis method. Meanwhile, we selected other three sensitivity analysis methods to examine the robustness of the IVW estimate. Results IVW analysis showed that the increased serum calcium level (per 1 standard deviation (SD) increase 0.5 mg/dL) was significantly associated with a reduced AD risk (OR = 0.57, 95% CI 0.35-0.95, p = 0.031). Meanwhile, all the estimates from other sensitivity analysis methods were consistent with the IVW estimate in terms of direction and magnitude. Conclusion In summary, we provided evidence that increased serum calcium levels could reduce the risk of AD. Meanwhile, randomized controlled study should be conducted to clarify whether diet calcium intake or calcium supplement, or both could reduce the risk of AD.

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders. In neurodegenerative diseases, O-GlcNAcylation of the brain's key proteins, such as tau and amyloid-β, interacts with their phosphorylation, thereby triggering the formation of neurofibrillary tangles and amyloid plaques. An increase of O-GlcNAcylation by pharmacological intervention prevents neuronal loss. Additionally, O-GlcNAcylation is stress sensitive, and its elevation is cytoprotective. Increased O-GlcNAcylation ameliorated brain damage in victims of both trauma-hemorrhage and stroke. In this review, we summarize the current understanding of O-GlcNAcylation's physiological and pathological roles in the nervous system and provide a foundation for development of a therapeutic strategy for neurological disorders.

Studies have suggested that heightened neuroinflammation contributes to the pathogenesis of depressive disorder. A major participant in neuroinflammation is microglia, and fractalkine signaling (which comprises the chemokine CX3CL1, mainly expressed by neurons, and its receptor CX3CR1, almost exclusively present on microglia in healthy brains) has been reported to critically regulate microglial activity. The aim of this study was to investigate whether CX3CR1 deficiency was associated with a different outcome following chronic unpredictable stress (CUS) and the possible mechanism. Wild-type (WT) and CX3CR1-deficient (CX3CR1-/-) mice were subjected to CUS for 3 weeks. CX3CR1-/- mice displayed a better performance through sucrose preference test, open field test and forced swim test, which demonstrated that CX3CR1 deficiency alleviated depressive-like disturbances, such as anhedonia, anxiety or hopelessness. Nevertheless, CX3CR1-/- mice also showed less severe cognitive impairment from the results of Morris Water Maze and Novel object recognition. Long-term potentiation was recorded to test the synaptic plasticity and its result was consistent with that of cognitive ability tests. Both results of real time-PCR and immunofluorescence staining demonstrated that CX3CR1 deficiency facilitated the alternative activation of microglia, thus attenuated the release of inflammatory cytokines, which was verified by ELISA and flow cytometry. Maybe due to the mitigated neuroinflammation, CX3CR1-deficient mice showed higher resilience to CUS-induced blood brain barrier hyperpermeability and loss of dendrite spine (as showed by Golgi and DiI staining) than WT group. All of above results indicated that hampering neuron-microglia communication via CX3CR1-CX3CL1 pathway attenuated the effects of CUS on depressive-like disturbances and cognitive impairment.

Estimating age through a single facial image is a classic and challenging topic in computer vision. Since facial images of the same age vary considerably, while those from different ages may look very similar. To address these problems, we propose an end-to-end deep embedding neural network for robust age estimation. Specifically, we jointly use classification loss and triplet-based ranking loss to train a deep embedding network, which maps the input facial images into an embedding metric space where features of the same age are compact and those from different ages are pushed away. Thus the deep embedding network can learn more discriminative features and improves the performance for age estimation. Additionally, to accelerate the convergence of the network, we adopt an online hard negative mining strategy during the triplet loss computation. Experimental results on public datasets MORPH II and FG-NET show the superiority of our approach compared to the state-of-the-art.

Background Post-traumatic Guillain-Barré syndrome (GBS) is a rarely described potentially life-threatening cause of weakness. We sought to elucidate the clinical features and electrophysiological patterns of post-traumatic GBS as an aid to diagnosis. Methods We retrospectively studied six patients diagnosed with post-traumatic GBS between 2014 and 2016 at Tianjin Medical University General Hospital, China. Clinical features, serum analysis, lumbar puncture results, electrophysiological examinations, and prognosis were assessed. Results All six patients had different degrees of muscular atrophy at nadir and in two, respiratory muscles were involved. Five also had damaged cranial nerves and four of these had serum antibodies against gangliosides. The most common electrophysiological findings were relatively normal distal latency, prominent reduction of compound muscle action potential amplitude, and absence of F-waves, which are consistent with an axonal form of GBS. Conclusions It is often overlooked that GBS can be triggered by non-infectious factors such as trauma and its short-term prognosis is poor. Therefore, it is important to analyze the clinical and electrophysiological features of GBS after trauma. Here we have shown that electrophysiological evaluations are helpful for diagnosing post-traumatic GBS. Early diagnosis may support appropriate treatment to help prevent morbidity and improve prognosis.

Recent studies suggest that microRNA-132 (miR-132) potentiates the cholinergic blockade of inflammatory reactions by targeting acetylcholinesterase (AChE) and affords robust protection against ischemia-induced neuronal death. However, the role of miR-132 in intracerebral hemorrhage (ICH) remains unexplored. This study aimed to determine whether miR-132 participates in the process and launches an anti-inflammatory response in a mouse model of ICH. To establish a relationship between miR-132 and ICH-induced neuronal inflammation and death, we used unilateral stereotaxic injections to deliver lentiviruses encoding miR-132, anti-miR-132 or an empty lentiviral vector directly into the right caudate nuclei of 192 living male C57BL/6 mice. Fourteen days later, ICH was induced by injection of autologous blood into these three groups. Neurodeficits, brain edema, blood-brain barrier (BBB) integrity, inflammatory reactions, together with cell death were assessed after ICH. Compared with the control group, the mice overexpressing miR-132 in the brain responded with attenuated neurological deficits and brain edema. The counts of activated microglia and the expression of proinflammatory cytokines were also decreased in these mice. Additionally, BBB integrity improved, and the extent of neuronal death decreased in ICH mice injected with lentivirus encoding miR-132. On the contrary, a decrease of miR-132 expression aggravated the severity of inflammation and increased cell apoptosis. Overall, these findings support a protective role of miR-132 in a mouse model of ICH, providing new opportunities for therapeutic intervention.

The advanced treatment and reuse of secondary effluent from urban sewage plants is currently one of the reliable ways to solve the shortage of urban water resources. This paper proposes a new type of enhanced flocculation and sedimentation process for the advanced treatment of secondary effluent from a wastewater treatment plant. The new type of enhanced flocculation sedimentation tank is used as a main process for new advanced wastewater treatment. The combination of wing micro vortex flocculation tank, net catching flocculation, inclined plate sedimentation tank and biological filter has good effluent quality. Basically, CODCr were stable at 35 mg/L, turbidity of effluent were stable at 2 NTU, chroma were stable at 30 degrees, TP were stable at 1 mg/L.

Inflammatory responses are accountable for secondary injury induced by acute ischemic stroke (AIS). Previous studies indicated that O-GlcNAc modification (O-GlcNAcylation) is involved in the pathology of AIS, and increase of O-GlcNAcylation by glucosamine attenuated the brain damage after ischemia/reperfusion. Inhibition of β-N-acetylglucosaminidase (OGA) with thiamet G (TMG) is an alternative option for accumulating O-GlcNAcylated proteins. In this study, we investigate the neuroprotective effect of TMG in a mouse model of experimental stroke. Our results indicate that TMG administration either before or after middle cerebral artery occlusion (MCAO) surgery dramatically reduced infarct volume compared with that in untreated controls. TMG treatment ameliorated the neurological deficits and improved clinical outcomes in neurobehavioral tests by modulating the expression of pro-inflammatory and anti-inflammatory cytokines. Additionally, TMG administration reduced the number of Iba1+ cells in MCAO mice, decreased expression of the M1 markers, and increased expression of the M2 markers in vivo. In vitro, M1 polarization of BV2 cells was inhibited by TMG treatment. Moreover, TMG decreased the expression of iNOS and COX2 mainly by suppressing NF-κB p65 signaling. These results suggest that TMG exerts a neuroprotective effect and could be useful as an anti-inflammatory agent for ischemic stroke therapy.

Background Microglia/macrophages play a critical role in the inflammatory and immune processes of cerebral ischemia/reperfusion injury. Since microglia/macrophages can reversibly shift their phenotype toward either a “detrimental” or a “restorative” state in the injured central nervous system (CNS), compounds mediate that shift which could inhibit inflammation and restore the ability to alleviate cerebral ischemia/reperfusion injury would have therapeutic potential. Methods Transient middle cerebral artery occlusion was induced in male C57BL/6 mice. Mice were randomly separated into a sham-operated group, a control group, and a ZSTK474-treated group. We investigated the effect of ZSTK474 by assessing neurological deficits, infarct volume, and histopathological changes. We then determined the potential mechanism by immunofluorescent staining, quantitative real-time polymerase chain reaction (PCR), and Western blot analysis. The Tukey’s test or Mann–Whitney U test was used to compare differences among the groups. Results ZSTK474 alleviated neurological deficits and reduced infarct volume in the cerebral ischemia/reperfusion injury model. Presumably, ZSTK474 shifted the phenotype of microglia/macrophages to a restorative state, since this treatment decreased the secretion of pro-inflammatory factors and advanced the secretion of anti-inflammatory factors. These neuroprotective properties of ZSTK474 may be mediated by the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway. Conclusions ZSTK474 can mediate a shift in microglia/macrophage phenotype and inhibit the inflammatory response in cerebral ischemia reperfusion injury of mice. These effects appeared to ensue via the PI3K/AKT/mTORC1 pathway. Therefore, ZSTK474 may represent a therapeutic intervention with potential for circumventing the catastrophic aftermath of ischemic stroke. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0660-1) contains supplementary material, which is available to authorized users.